The principal objectives of this project are to continue the investigations already begun in this laboratory on the hormone prolactin and on other pituitary and hypothalamic hormones whose secretion or action may be related to that of prolactin. Specifically proposed are studies on prolactin's role in certain neoplasms, including pituitary tumors and cancer of the breast. The effects of prolactin-lowering drugs and other modes of therapy will be studied in patients with prolactin-secreting tumors with respect to their effects on prolactin secretion, tumor size, and reproductive function. Studies of prolactin receptors in tissue specimens from patients with cancer of the breast will be continued and correlated with estrogen and progesterone receptor data and with clinical course and response to therapy. A major portion of this project will be devoted to studies of B-endorphin and related peptides. Specifically these will include studies of B-endorphin as possible regulator of anterior pituitary function, with particular emphasis on prolactin and gonadotropins. The methodology will include the use of stalk-sectioned monkeys and the examination of the effects of sex steroid administration on hypophyseal portal blood content of B-endorphin. The regulation and secretion of B-endorphin will be studied in patients with adrenal disorders and compared with that of ACTH. The effects of stress and chronic narcotic administration on brain B-endorphin content and processing will be studied in rats. Fetal secretion and regulation of B-endorphin will be examined in the sheep and compared with that of the mother by means of chronically catheterized ewes and their fetuses. The general aim of these studies is a broader understanding of hypothalamic and pituitary function in normal and diseased states.